Transcriptomic Analysis of Wuzi Yanzongwan on Testicular Spermatogenic Function in Semi-castrated Male Mice / 中国实验方剂学杂志

ObjectiveTo screen out the transcriptomes related to the intervention of Wuzi Yanzongwan on the spermatogenic function of semi-castrated male mice， and to explore its potential mechanism in the intervention of the progress of low spermatogenic function. MethodBalb/c mice were randomly divided into sham-operated group， model group， testosterone propionate group（0.2 mg·kg-1·d-1， intramuscular injection） and Wuzi Yanzongwan group（1.56 g·kg-1·d-1， intragastric administration） according to body weight， with 12 mice in each group. The right testicle and epididymis were extracted from the model group and the drug administration group to construct the semi-castrated model of low spermatogenic function， while the fur and the right scrotum of the sham-operated group were only cut and immediately sterilized and sutured. At the end of the intervention， hematoxylin-eosin（HE） staining was used to observe the histopathology of testis， enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of serum testosterone（T）， luteinizing hormone（LH） and follicle stimulating hormone（FSH）. The sperm count and motility of epididymis were measured by automatic sperm detector of small animal. Transcriptomic microarray technology was used to detect the mRNA expression level of testicular tissue in each group， the transcriptome of genes related to the regulation of Wuzi Yanzongwan was screened， and three mRNAs were selected for Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） to verify the transcriptome data. Through the annotation analysis of Gene Ontology（GO） and the signaling pathway analysis of Kyoto Encyclopedia of Genes and Genomes（KEGG）， the related functions of drugs regulating transcriptome were analyzed. ResultCompared with the sham-operated group， the testicular tissue of mice in the model group showed spermatogenic injury， contraction and vacuolization of the seminiferous tubules， reduction of spermatogenic cells at all levels， widening of the interstitial space， obstruction of spermatogonial cell development and other morphological abnormalities， and serum T significantly decreased， LH significantly increased（P<0.01）， and FSH elevated but no statistically significant difference， the count and vitality of epididymal sperm significantly decreased（P<0.01）. There were 882 differentially expressed mRNAs in the testicular tissues， of which 565 were up-regulated and 317 were down-regulated. Cluster analysis showed that these differentially expressed mRNA could effectively distinguish between the sham-operated group and the model group. Compared with the model group， the damage to testicular tissue in the Wuzi Yanzongwan group was reduced， the structure of the seminiferous tubules was intact， vacuolization was reduced， and the number of spermatogenic cells at all levels was significantly increased and arranged tightly. The serum T significantly increased， LH significantly decreased（P<0.01）， and FSH decreased but the difference was not statistically significant. The count and vitality of sperm in the epididymis were significantly increased（P<0.01）. Moreover， Wuzi Yanzongwan could regulate 159 mRNA levels in the testes of semi-castrated mice， of which 32 were up-regulated and 127 were down-regulated， and the data of the transcriptome assay was verified to be reliable by Real-time PCR. GO and KEGG analysis showed that the transcriptome functions regulated by Wuzi Yanzongwan were involved in the whole cell cycle process of sperm development such as sex hormone production of interstitial cells in testis， renewal， differentiation， metabolism， apoptosis and signal transduction of spermatogenic cells， and were closely related to the biological behaviors of signaling pathways such as spermatogenic stem cell function， endoplasmic reticulum protein processing and metabolic program. ConclusionWuzi Yanzongwan can effectively improve the low spermatogenic function of semi-castrated male mice， and its mechanism may be related to the regulation of testicular transcriptional regulatory network， the synthesis of sex hormones in testicular interstitial cells， the function of spermatogenic stem cells， the whole cell cycle process of spermatogenesis， as well as the expression of endoplasmic reticulum protein processing and metabolic program related genes transcription.

Pharmacokinetic investigation of principal active constituents in renal fibrotic rats after oral administration of crude and salt-processed eucommiae cortex extracts / 药学学报

A quantitative analysis method for six principal active constituents (acubin, geniposidic acid, chlorogenic acid, pinoresinol di-O-glucopyranoside, geniposide, and pinoresinol 4-O-glucopyranoside) of crude Eucommiae Cortex (EC) and its salt-processed product extracts was developed to investigate and compare their pharmacokinetic behaviors in adenine-induced renal fibrotic rats in vivo. UHPLC-QqQ-MS/MS technology was employed. Scan was conducted in negative ion mode and quantitative determination was carried out by MRM paired ion. The established method was fully validated by specificity, linearity, precision, accuracy, stability, recovery, and matrix effect, and the results of methodological investigation met the requirements of biological sample analysis. Then, a quick, sensitive, and accurate method was successfully established, which could simultaneously measure the contents of six active constituents of crude and salt-processed EC extracts in rat plasma. After a single administration to renal fibrotic rats of crude EC and its salt-processed product extracts, the plasma concentration of each constituent at different time points was measured, the pharmacokinetic parameters were calculated and the concentration time curves were structured. The experiment was approved by the experimental animal ethics committee from Nanjing University of Chinese Medicine (No. 202103A008). The results showed that compared to the crude Eucommiae Cortex group, the tmax of aucubin, pinoresinol di-O-glucopyranoside, geniposide, and pinoresinol 4-O-glucopyranoside in the salt-processed Eucommiae Cortex group rat plasma were significantly lower than those in the crude group (P < 0.05, P < 0.01); the Cmax and AUC0-48 h of chlorogenic acid, the Cmax, AUC0-48 h and AUC0-∞ of pinoresinol di-O-glucopyranoside, and the Cmax of geniposide and pinoresinol 4-O-glucopyranoside were significantly higher than those in the crude group (P < 0.05, P < 0.01). Our investigation found that compared to crude Eucommiae Cortex, a variety of active ingredients could play a role of quick effect with higher peak blood concentration and bioavailability after oral administration of salt-processed Eucommiae Cortex, which were consistent with the traditional Chinese medicine theory of "salt-processing enhancing drug into kidney meridian", providing an experimental basis for the selection of quality control indexes and the in-depth study of processing mechanisms and metabolic rules in vivo of Eucommiae Cortex and its salt-processed product.

Integration of plasma metabolomics and spectrum-effect correlation for profiling the mechanism and pharmacodynamic substances on attenuating hepatic fibrosis of Bupleuri Radix and Paeoniae Radix Alba before and after vinegar-processing and compatibility / 药学学报

Plasma metabolomics based on UHPLC-Q-TOF-MS/MS technique was developed for profiling the mechanism on attenuating hepatic fibrosis of Bupleuri Radix (BR) and Paeoniae Radix Alba (PRA) before and after vinegar-processing and compatibility, and to screen potential pharmacodynamic substances by spectrum-effect correlation method in this study. Firstly, SD rats with CCl4-induced hepatic fibrosis were used as an in vivo model. The blood and tissue samples were collected for the analyses of pharmacodynamic indexes and plasma metabolomics after six weeks’ administration of BR, vinegar-processed BR (VPBR), PRA, vinegar-processed PRA (VPPRA), BR-PRA herb-pair, and VPBR-VPPRA herb-pair. The experiment was approved by the experimental animal ethics committee from Nanjing University of Chinese Medicine (No.202103A002). The results of pharmacodynamics indicated that the levels of alanine aminotransferase (ALT, P < 0.01), aspartate aminotransferase (AST, P < 0.01), and hydroxyproline (HYP, P < 0.01) were decreased significantly, while the level of glutathione peroxidase (GSH-Px, P < 0.05) was increased obviously after administration of all treatment groups. Next, UHPLC-Q-TOF-MS/MS was performed to characterize the endogenous metabolites. A total of 20 differential endogenous metabolites related to the pathogenesis of hepatic fibrosis were identified in positive and negative ion modes, mainly involving five metabolic pathways of retinol metabolism, glycerol phospholipid metabolism, glyceride metabolism, fatty acid biosynthesis, and arachidonic acid metabolism. Meanwhile, a concept named correction rate was introduced to evaluate the back-regulation effects of all treatment groups on differential metabolites, and 10 differential metabolites were corrected by all treatment groups. The correction effects of the vinegar-processed herb groups were better than those of the crude ones, and the correction effects of the herb-pair groups were better than those of the single ones. Interestingly, the best correction effect was found in the VPBR-VPPRA herb-pair group, which further verified the efficacy improvement through vinegar-processing and compatibility. Partial least square method and VIP analysis combined with spectrum-effect correlation were applied for screening pharmacodynamic markers, and 38 ingredients with higher correlation with four classical pharmacodynamic indexes (ALT, AST, HYP, and GSH-Px) were identified as pharmacodynamic markers of the anti-hepatic fibrosis effects of BR and PRA before and after vinegar-processing and compatibility. The results of the investigation could not only lay a foundation for clarifying the pharmacodynamic materials and mechanism of vinegar-processing and compatibility of BR and PRA in the treatment of hepatic fibrosis as well as provide a theoretical basis for demonstrating the scientific connotation of processing and compatibility, but also provide a reference for further drug design and development of BR and PRA in clinic.

Circular RNA_0003028 targeting microRNA-498 regulating the effects of suppressor with morphogenesis effect on genitalia-l/p53 signaling pathway on liver cancer cell line Huh7 / 解剖学报

Objective To investigate the effects and molecular mechanism of circular RNA (circ) _0003028 on proliferation, migration and invasion of human liver cancer cells. Methods Liver cancer cell line Huh7 were divided into small interfering RNA(si)-NC group, si-circ_0003028 group, microRNA(miR) -NC group, miR-498 mimics group, si-circ _0003028+anti-miR-NC group and si-circ_0003028+anti-miR-498 group. Real-time PCR was used to detect the expression levels of circ _ 0003028 and miR-498 in liver cancer tissues and cells of each groups. MTT was used to detect cell proliferation. Transwell was used to detect cell migration and invasion. Western blotting was used to detect protein expression. Dual luciferase reporter experiment was used to detect the target regulation relationship between circ_0003028 and miR-498. Results The expression level of circ_0003028(0.98±0.02 vs 1. 36±0. 01) increased and the expression level of miR-498(0. 98±0. 02 vs 0. 63±0. 02) decreased in liver cancer tissues (P<0. 05). After inhibiting the expression of circ_0003028 or overexpression of miR-498- the expression levels of Ki-67(0. 85±0. 02 vs 0. 41±0. 02 or 0. 95±0. 11 vs 0. 37±0. 02)- matrix metalloprotein(MMP)-2(0. 71±0. 02 vs 0. 43±0. 03 or 0. 83±0. 02 vs 0. 41±0. 03)- and MMP-9 (0. 74±0. 02 vs 0. 37±0. 02 or 0. 78±0. 02 vs 0. 39±0. 02) proteins in Huh7 cells decreased- and cell viability(1. 53± 0. 03 vs 1. 05±0. 02 or 1. 68±0. 02 vs 1. 11±0. 02) decreased- the number of migration(111. 40±2. 12 vs 77. 22±2. 38 or 108. 90±2. 30 vs 78. 44 ± 1. 46) and invasion ( 87. 89 ± 2. 18 vs 49. 78 ± 1. 98 or 80. 22 ± 1. 79 vs 38. 22 ± 1. 52) cells decreased- and the protein expression levels of suppressor with morphogenesis effect on genitalia-1( SMG-1) (0. 76±0. 02 vs 1. 39±0. 02 or 0. 79±0. 02 vs 1. 39±0. 02)- p53(0. 77±0. 02 vs 1. 24±0. 03 or 0. 82±0. 03 vs 1. 45±0. 03)- and p53- ser15(0. 78±0. 03 vs 1. 50±0. 02 or 0. 82±0. 02 vs 1. 49±0. 04) increased (P<0. 05). circ_0003028 targeted regulation of miR-498- and silencing miR-498 reversed the effects of inhibiting the expression of circ_0003028 on the proliferation- migration and invasion of Huh7 cells. Conclusion Inhibiting the expression of circ_0003028 can inhibit the proliferation- migration and invasion of liver cancer cells by targeting miR-498 to affect the SMG-1/ p53 signaling pathway.

The protective effects of sinomenine on organotin-injured liver HL02 cells and its mechanism / 中国药理学通报

Aim To investigate the protective effect of sinomenine(SIN)against dibutyltin(DBT)induced injury in HL02 cells and explore the potential mechanism.Methods HL02 cells were cultured and divided into control,model and SIN-treated groups.Cell proliferation was detected by MTT method.Cell morphology was observed.Cell apoptosis was detected by Acridine orange/ethidium bromide(AO/EB)fluorescent staining and Annexin V-FITC/PI double staining.Meanwhile,intracellular reactive oxygen species(ROS)concentration was detected by DCFH-DA staining.Mitochondrial membrane potential(MMP)was tested by JC-1 dye.Moreover,the mRNA expression of apoptosis-related proteins was detected by qRT-PCR,and the protein expression of Bcl-2,Bax,caspase-9,cleaved-caspase-3 were measured via Western blot.Results The pretreatment with SIN increased the cell viability and decreased morphological changes induced by DBT in a dose-dependent manner.Meanwhile,cell apoptotic rates and intracellular ROS decreased,and the loss of MMP was partially restored.Compared to DBT-treated group,SIN treatment could increase the mRNA levels of Bcl-2,Bcl-xL and decrease the mRNA levels of Bax,Bad,cytochrome-c,Apaf-1,caspase-9 and caspase-3.Furthermore,SIN could significantly up-regulated the DBT-induced decrease in Bcl-2/Bax ratio,and down-regulated the DBT-induced over-expressions of caspase-9 and cleaved-caspase-3.Conclusions SIN could protect HL02 cells against DBT-induced cell injury,which is related to the inhibition of ROS-mediated mitochondrial apoptosis.

Systematic review and Meta-analysis on efficacy and safety of Naoxueshu Oral Liquid in treatment of hypertensive intracerebral hemorrhage / 中国中药杂志

To systematically review the efficacy and safety of Naoxueshu Oral Liquid in treatment of hypertensive intracerebral hemorrhage, four Chinese databases, four English databases, clinical trials registration center(ClinicalTrials.gov) and Chinese clinical trial registry were retrieved. The retrieval time was from the establishment of each database to September 9, 2020. According to the set criteria, the randomized controlled trial(RCT) of Naoxueshu Oral Liquid combined with conventional Western medicine was selected. The "Cochrane bias risk assessment" tool was used to evaluate the quality of the included studies. RevMan 5.4.1 was used to conduct Meta-analysis of the included studies and GRADE system was used to evaluate the evidence quality of the outcome indicators. Eleven studies were finally included, with a total sample size of 1 221 cases, 612 cases in the treatment group and 609 cases in the control group. Meta-analysis showed that Naoxueshu Oral Liquid combined with conventional Western medicine had no significant difference compare with conventional Western medicine in reducing National Institute of health stroke scale(NIHSS) after 2 weeks of treatment for hypertensive intracerebral hemorrhage(MD=-1.59,95%CI[-3.46,0.29],P=0.10), but was superior to conventional Western medicine after 30 d of treatment(MD=-1.16,95%CI [-1.39,-0.94],P<0.000 01). Naoxueshu Oral Liquid combined with conventional Western medicine was superior to conventional Western medicine in improving Glasgow coma scale(MD=1.00,95%CI[0,2.00],P=0.05) and reducing the incidence of secondary brain insults(RR=0.38,95%CI[0.24,0.59],P<0.000 1), but there was no significant difference in increasing Barthel index(MD=1.00,95%CI[-0.30,2.30],P=0.13). In terms of effective rate, studies using Guideline for clinical trials of new patent Chinese medicines, NHISS or Glasgow outcome scale(GOS) had shown that Naoxueshu Oral Liquid combined with conventional Western medicine was superior to conventional Western medicine(RR_(Guideline for clinical trials of new patent Chinese medicines)=1.27,95%CI[1.10,1.46],P=0.001;RR_(NHISS)=1.26,95%CI[1.13,1.40],P<0.000 1;RR_(GOS)=1.54,95%CI[1.22,1.93],P=0.000 2). In reduction of hematoma volume, Naoxueshu Oral Liquid combined with conventional Western medicine was superior to conventional Western medicine after 2 and 4 weeks of treatment(MD_(2 week)=-2.31,95%CI[-3.12,-1.49],P<0.000 01;MD_(4 week)=-2.04,95%CI[-2.41,-1.68],P<0.000 01). GRADE system showed that the evidence level of the above outcome indicators was low and extremely low. In terms of adverse reactions, two of the included studies reported mild adverse reactions, and the rest of studies were not mentioned, so this study was not able to make a positive evaluation of the safety of Naoxueshu Oral Liquid. This study showed that compared with conventional Western medicine, combined Naoxueshu Oral Liquid may be better for hypertensive intracerebral hemorrhage. However, due to the high bias risk in the included studies, more large-sample and high-quality RCTs are still needed in the future.

Clinical study of periodontal endoscope-assisted subgingival scaling in the treatment of residual pocket / 华西口腔医学杂志

OBJECTIVES@#To compare the treatment effects of periodontal endoscope-assisted and traditional subgingival scaling on residual pockets.@*METHODS@#A total of 13 patients with periodontitis from Dept. of Periodontics, West China Hospital of Stomatology, Sichuan University were recruited. After 4-6 weeks of initial treatment, the residual pockets with a probing depth (PD) of ≥4 mm and attachment loss (AL) of ≥4 mm and bleeding on probing were examined with traditional (control group) and periodontal endoscope-assisted subgingival scaling (endoscopy group) in a randomly controlled split-mouth design. At baseline and 6 weeks and 3 months after treatment, plaque index (PLI), PD, AL, and bleeding index (BI) were measured. Differences in these clinical parameters within and between groups and patient-reported outcomes were compared.@*RESULTS@#A total of the 694 sites of 251 teeth were included in this trial. Both groups showed significant improvement in each periodontal parameters 6 weeks and 3 months after treatment (@*CONCLUSIONS@#Periodontal endoscope-assisted subgingival scaling resulted in better effects than traditional subgingival scaling when the residual pockets were in a single-rooted tooth, with a PD of ≥5 mm but without vertical alveolar bone resorption and furcation involvement.

Mechanism investigation on the enhanced anti-hepatic fibrosis effects in rats of Fructus Corni after wine-processing based on plasma metabonomics / 药学学报

Metabonomics technology was employed to investigate and identify the mechanisms and metabolic pathways of the crude and wine-processed Fructus Corni extracts on anti-hepatic fibrosis effects in rats, and to compare and analyze the potential mechanism of enhanced interference of the wine-processed Fructus Corni on hepatic fibrosis effects in rats. The rats were randomly divided into the blank control group, the model group, the colchicine group, the crude Fructus Corni groups with low, medium, and high-doses, and the wine-processed Fructus Corni groups with low, medium, and high-doses, and there were six rats in each group. The hepatic fibrosis model was established by subcutaneous injection of 40% carbon tetrachloride, and the intragastric administration was performed at the third week of modeling. The blood and liver samples of rats were taken and carried out for pharmacodynamic index detection and UHPLC-Q-TOF-MS/MS analysis after intragastric administration for six weeks. The results of pharmacodynamic investigation showed that both the crude and wine-processed Fructus Corni had the effects of anti-hepatic fibrosis in rats. Metabonomics analysis indicated that, compared to the blank control group, the twenty-four potential biomarkers related to hepatic fibrosis were screened and identified in the model group, which mainly involved in primary bile acid metabolism, glycerol phospholipid metabolism, pentose and glucuronide metabolism, retinol metabolism, and arachidonic acid metabolism. The crude and wine-processed Fructus Corni extracts had different degrees of callback effects on the ten of the above potential biomarkers, and the effect of wine-processed Fructus Corni was better than that of crude one. The present study clarifies the mechanism of enhanced efficiency of wine-processed Fructus Corni from the perspective of plasma metabolism, and provides the theoretical foundation for further development and clinical application of Fructus Corni.

Systematic review and Meta-analysis of efficacy and safety of acupuncture therapy on hypertensive intracerebral hemorrhage / 中国中药杂志

To systematically review the efficacy and safety of acupuncture combined with minimally invasive surgery or basic the-rapy in treating hypertensive intracerebral hemorrhage(HICH) patients compared with minimally invasive surgery or basic treatment. In this study, the four Chinese databases, the four English databases, Chinese Clinical Trial Registry and ClinicalTrail.gov, all above were systematically and comprehensively retrieved from the time of database establishment to September 10, 2020. Rando-mized controlled trials(RCTs) were screened out according to inclusion criteria and exclusion criteria established in advanced. The methodological quality of included studies was evaluated by the tool named "Cochrane bias risk assessment 6.1". Meta-analysis of the included studies was performed using RevMan 5.4, and the quality of outcome indicators was evaluated by the GRADE system. Finally, 17 studies were included, involving 1 852 patients with HICH, and the overall quality of the included studies was not high. According to Meta-analysis,(1)CSS score of the group of acupuncture combined with minimally invasive surgery or basic therapy was superior to the group of minimally invasive surgery or basic therapy(MD=-3.50,95%CI[-4.39,-2.61],P<0.000 01);(2)NIHSS score of the group of acupuncture combined with minimally invasive surgery or basic therapy was superior to the group of minimally invasive surgery or basic therapy(MD=-4.78,95%CI[-5.55,-4.00],P<0.000 01);(3)the cerebral hematoma volume of the group of acupuncture combined with minimally invasive surgery or basic therapy was superior to the group of minimally invasive surgery or basic therapy(MD=-4.44,95%CI[-5.83,-3.04],P<0.000 01);(4)ADL score of the group of acupuncture combined with minimally invasive surgery or basic therapy was superior to the group of minimally invasive surgery or basic therapy(MD=20.81,95%CI[17.25,24.37],P<0.000 01);(5)the GCS score of the group of acupuncture combined with minimally invasive surgery or basic therapy was superior to the group of minimally invasive surgery or basic therapy(MD=2.41,95%CI[1.90,2.91],P<0.000 01). The GRADE system showed an extremely low level of evidence for the above outcome indicators. Adverse reactions were mentioned only in two literatures, with no adverse reactions reported. The available evidence showed that acupuncture combined with minimally invasive surgery or basic therapy had a certain efficacy in patients of HICH compared with minimally invasive surgery or basic therapy. However, due to the high risk of bias in the included studies, its true efficacy needs to be verified by more high-quality studies in the future.

Overview of systematic reviews/Meta-analysis of Xingnaojing Injection in treatment of intracerebral hemorrhage / 中国中药杂志

To overview of systematic reviews/Meta-analysis of Xingnaojing Injection(XNJ) in the treatment of intracerebral hemorrhage(ICH). The systematic reviews concerning XNJ in the treatment of ICH were retrieved from four Chinese databases, four English databases, Chinese Clinical Trial Registry and ClinicalTrail.gov, with the retrieval time set from their inception to September 2020. Following the independent screening and data extraction by two researchers, a measurement tool to assess systematic evaluation 2(AMSTAR 2) and grades of recommendation, assessment, development and evaluation(GRADE) system were used to evaluate the metho-dological, reporting and evidence qualities of the 10 included systematic reviews. The results showed that XNJ was superior to the wes-tern medicine or conventional treatment in improving the effective rate and National Institutes of Health stroke scale(NIHSS) score, Barthel index(BI), and Glasgow coma scale(GCS) score and Chinese stroke scale(CSS) score, and reducing the mortality and cerebral hematoma volume, without inducing obvious adverse reactions. In general, the methodological, reporting and evidence qualities of the 10 included systematic reviews were poor. The AMSTAR 2 scores showed that key items No. 2 and No. 16 failed to meet the stan-dard, resulting in poor methodological quality. There was only one outcome indicator graded by GRADE as intermediate quality, 43% indicators as low quality, 42% indicators as extremely low quality, and none as high quality. These available evidences have suggested that the methodological, reporting and evidence qualities of the systematic evaluation concerning XNJ for the treatment of ICH need to be improved. Most evidences support that XNJ was better than the western medicine or conventional treatment in the treatment of ICH, but the methodological quality and the reliability of outcome indicators in relevant systematic review were low. More high-quality studies are still required for further verification.

Situation analysis of outcome indicators of randomized controlled trials of traditional Chinese medicine in treatment of hypertensive intracerebral hemorrhage in recent three years / 中国中药杂志

The study aims to analyze the outcome indicators of randomized controlled trial(RCT) of traditional Chinese medicine(TCM) in the treatment of hypertensive intracerebral hemorrhage(HICH) in recent three years, and thus provide suggestions for the future studies in this field. Four English databases, four Chinese databases and two online registration websites of clinical trials were searched. The RCTs published between January 2018 and September 2020 were screened. The risk of bias was assessed and outcome measures were classified. A total of 151 839 articles were retrieved, of which 44 RCTs were included for analysis after screening. The outcome measures of the included RCTs were classified into 7 categories, among which the symptoms/signs category showed the highest reporting rate. National Institute of Health stroke scale(72.73%) was the most frequently reported outcome indicator, while the vo-lume of intracerebral hemorrhage determined by computerized tomography(36.36%) was the most frequently reported lab test outcome. Most studies collect the outcomes at the end of treatment, while 9 studies reported long-term outcomes 3 months or more after onset. Compared with those of international clinical trials, the application of some of the outcomes was reasonable, focusing on patients' symptoms, quality of life and objective outcomes. However, there were still several problems: unclear primary and secondary outcome measures, insufficient attention to long-term prognosis, insufficient attention to social function, few TCM outcomes, lack of measurement blindness and the use of unreasonable composite outcomes. It is recommended that researchers should rationally design the outcome indicators of clinical trials and develop the core outcome set.

Simultaneous quantitative analysis of nine saponins in Gynostemma pentaphyllum before and after heat processing based on UPLC-Q-Trap-MS / 中国中药杂志

Heat-processed Gynostemma pentaphyllum has strong biological activity, and saponins are the main components. To investigate the changes of saponins in G. pentaphyllum before and after heat processing, the present study determined and analyzed the content of nine saponins in G. pentaphyllum from Zhangzhou of Fujian and Jinxiu of Guangxi by ultra-high performance liquid chromatography with quadrupole ion-trap mass spectrometry(UPLC-Q-Trap-MS). The separation of the analytes was performed on an ACQUITY UPLC BEH C_(18) column(2.1 mm×50 mm, 1.7 μm) at 30 ℃, with acetonitrile and 0.1% formic acid in water as the mobile phase by gradient elution, and the flow rate was 0.3 mL·min~(-1). Quantitative analysis was performed using electrospray ionization source(ESI) in the multiple reaction-monitoring(MRM) mode. The results showed that the content of saponins with biological activities increased after heat processing. Specifically, gypenoside L, gypenoside LI, damulin A, damulin B, ginsenoside Rg_3(S), and ginsenoside Rg_3(R) in G. pentaphyllum produced in Zhangzhou of Fujian increased by 7.369, 8.289, 12.155, 7.587, 0.929, and 1.068 μg·g~(-1), respectively, while the content of ginsenoside Rd, gypenoside LVI, and gypenoside XLVI, which were abundant in the raw materials, decreased by 0.779, 19.37, and 9.19 μg·g~(-1), respectively. The content of gypenoside L, gypenoside LI, damulin A, damulin B, ginsenoside Rg_3(S), and ginsenoside Rg_3(R) in G. pentaphyllum produced in Jinxiu of Guangxi increased by 0.100, 0.161, 0.317, 0.228, 3.280, and 3.395 μg·g~(-1), respectively, while the content of ginsenoside Rd, gypenoside LVI, and gypenoside XLVI in the raw materials was reduced by 1.661, 0.014, and 0.010 μg·g~(-1), respectively. The results suggest that heat processing is an effective way to transform rare gypenosides. Furthermore, it is found that there are great differences in the content of gypenosides in different regions.

Roles of processing and compatibility in antidepression of Sini Powder:a metabonomics study / 中国中药杂志

The antidepressant mechanism of Sini Powder was investigated by metabonomics based on UHPLC-Q-TOF-MS, and the roles of processing and compatibility in the antidepression of Sini Powder were discussed in the present study. The chronic unpredictable mild stress(CUMS) model of depression was induced in the model group, the Bupleuri Radix group, the Paeoniae Radix Alba group, the herb-pair group(Bupleuri Radix-Paeoniae Radix Alba), the Sini Powder group, and the vinegar-processed Sini Powder group(Bupleuri Radix and Paeoniae Radix Alba were vinegar-processed). After the establishment of the model, the rats in each group were continuously administered with corresponding drugs(ig) at a dose of 9.6 g·kg~(-1) for eight days [the rats in the model group and the normal group(without model induction) received the same volume of normal saline at the same time]. Following the last administration, the differential metabolites were identified to analyze metabolic pathways based on the rat plasma samples collected from each group. A total of sixteen potential biomarkers were identified. The metabolites with significant changes were involved in many biological metabolic pathways, such as amino acid metabolism, pentose phosphate pathway, glycerol phospholipid metabolism, sphingolipid metabolism, and purine metabolism. After drug intervention, some biomarkers returned to normal levels. Further comparisons of processing and compatibility revealed that the vinegar-processed Sini Powder group had the most total metabolic pathways where differential metabolites were returned to normal. Compared with the individual herbs, the herb-pair significantly improved the recovery of differential metabolites in the pentose phosphate and purine metabolic pathways. Compared with the Sini Powder, the vinegar-processed Sini Powder facilitated the recovery of differential metabolites in the arginine biosynthesis, and pyrimidine and pentose phosphate metabolic pathways. As indicated by the results, Sini Powder may interfere with depression by regulating lipid and nucleotide metabolisms. The processing and compatibility of Chinese herbal medicines can potentiate the intervention on depression by regulating nucleotide, energy, and amino acid metabolisms to a certain extent.

Multimodal Analgesia of Enhanced Recovery after Surgery Management in Lobectomy by Video-assisted Thoracoscopic Surgery / 中国医学科学院学报

Video-assisted thoracoscopic surgery(VATS)has become the main method of lobectomy.Multimodal analgesia is one of the core contents of enhanced recovery after surgery(ERAS)management in VATS lobectomy,which aims to control perioperative pain,reduce stress response,and achieve rapid recovery after surgery.In recent years,multimodal analgesia has developed rapidly,emphasizing the comprehensive implementation of a variety of analgesic methods and the synergistic application of analgesics with different mechanisms.This article reviews the new progress in the implementation of multimodal analgesia in VATS lobectomy and addresses the current problems and challenges,aiming to help develop more effective and practical analgesic strategies of ERAS.

Analysis on epidemiological and spatio－temporal characteristics of hand，foot and mouth disease in Yunnan Province from 2014 to 2018 / 中华疾病控制杂志

@#Objective To analyze the epidemic situation and characteristics of spatial autocorrelation and spatiotemporal regular of hand，foot and mouth disease( HFMD) in Yunnan Province during the period from 2014 to 2018，thus to provide theoretical basis for HFMD prevention and control． Methods Descriptive epidemiologic method was used to analyze the epidemic situation of HFMD，spatial autocorrela- tion was used to analyze the spatial cluster aggregation，and discrete Possion model in spatio－temporal in scan was used to detect HFMD＇s spatio－temporal clustering condition． Ｒesults The incidence of HFMD in Yunnan Province had been risen rapidly during the past 5 years． Cases mainly occurred among the group of male，0－4 years old group and scattered children． The predominant pathogen had changed，Other enterovir- us gradually replaced enterovirus 71( EV71) to be the predominant． HFMD cases and pathogen showed sig- nificant spatial clustering aggregation，HFMD cases hot spots mainly concentrated in the central and south－ central part of Yunnan Province． The amount of EV71 cases hot spots increased gradually，and the hot spot areas augmented and extended to the central and south－central part of Yunnan Province． There was obvious spatial－temporal aggregation of HFMD，annual scan results detected 3 first－level cluster areas and 1 second －level cluster area． Clustering time was mainly concentrated in April to October of each year． Conclusions Distribution characteristics of HFMD among people in Yunnan Province did not change significantly during the period from 2014 to 2018，while the proportion of pathogenic spectrum changed significantly． The key areas of HFMD control and prevention were still in the central and central－south part of Yunnan Province，while the aggregation and break of HFMD in these areas from April to October should be concerned．

Quantitative assessment of hemodynamics in patients with moyamoya disease before and after revascularization on phase-contrast magnetic resonance imaging / 国际脑血管病杂志

Objective:To evaluate the hemodynamics of patients with moyamoya disease before and 6 months after cerebral revascularization using phase-contrast magnetic resonance imaging (PC-MRI), and to analyze the risk factors for postoperative cerebral hyperperfusion syndrome (CHS).Methods:Patients with moyamoya disease underwent combined revascularization in Huadong Hospital Affiliated to Fudan University from January 2017 to April 2019 were enrolled retrospectively. PC-MRI was performed before and 6 months after surgery. The blood flow velocity, blood flow and the region of interest (ROI) area of the vascular lumen in internal carotid artery, external carotid artery, superficial temporal artery and vertebral artery were recorded. Multivariate logistic regression analysis was used to determine the independent correlated factors of CHS. Results:A total of 80 patients with moyamoya disease were included, including 35 males (43.75%), aged 42.4±10.1 years (range 19-60 years). The blood flow velocity ( P<0.05), blood flow ( P<0.01) and area of ROI ( P<0.01) of the superficial temporal artery were significantly increased at 6 months after surgery compared with the before surgery, and the blood flow of the vertebral artery was slower compared with the before surgery ( P<0.05). Univariate analysis showed that diabetes, predominant hemispheric operation, preoperative increased superficial temporal artery blood flow rate, reduced internal carotid artery flow, and increased external carotid artery flow were the possible risk factors for occurring CHS in patients with moyamoya disease after surgery. Multivariate logistic regression analysis showed that the predominant hemispheric operation (odds ratio [ OR] 4.627, 95% confidence interval [ CI] 1.019-21.009; P=0.047), preoperative superficial temporal artery blood flow ( OR 1.208, 95% CI 1.053-1.387; P=0.007) and external carotid artery blood flow ( OR 0.139, 95% CI 0.027-0.719; P=0.019) were independently associated with postoperative CHS. Conclusions:PC-MRI can evaluate the hemodynamic parameters of intracranial and extracranial major blood vessels, and it can be used as one of the important basis to evaluate the postoperative risk of moyamoya disease.

Effect of concentrated growth factors combined with guided tissue regeneration in treatment of classII furcation involvements of mandibular molars / 北京大学学报(医学版)

OBJECTIVE@#Tissues loss due to periodontal disease is typically treated by a variety of regenerative treatment modalities, including bone grafts, guided tissue regeneration (GTR) and growth factors, to reform the supporting tissues of teeth. Concentrated growth factors (CGF) are produced by centrifuging blood samples at alternating and controlled speeds using a special centrifuge. The purpose of this study was to evaluate whether GTR could improve the effect of CGF combined with bone graft in the treatment of classII furcations of mandibular molars.@*METHODS@#In the present study, thirty-five classII furcation involvements were included and randomly divided into two groups. The experimental group (n=17) accepted GTR combined with CGF and bone graft therapy, and the controlled group (n=18) accepted CGF combined with bone graft therapy. The clinical examinations and cone beam computed tomography (CBCT) were performed at baseline and 1 year post-surgery. Comparisons of clinical and CBCT data before and after operation between the experimental group and the control group were made.@*RESULTS@#The clinical and CBCT data of both groups were not statistically different at baseline (P>0.05). At the end of 1 year post-surgery, the clinical parameters of both groups were significantly improved (P<0.001). The probing depths of the experimental group were (4.81±1.95) mm and (3.56±1.94) mm, respectively, significantly higher than the changes of the control group (P<0.001). The vertical and horizontal attachment gains of the experimental group were (4.11±1.98) mm and (3.84±1.68) mm, respectively, significantly higher than the changes of the control group (P<0.001). At the end of 1 year post-surgery, the experimental group showed significantly higher bone gain at vertical and horizontal directions compared with those of the control group: (3.84±1.68) and (3.88±2.12) mm, respectively (P<0.001).@*CONCLUSION@#Within the limitation of the present study, GTR showed positive role in the effect of CGF combined with bone graft in the treatment of classII furcation involvements of mandibular molars.

Associations of impaired glucose metabolism with chronic peridontitis in pre-diabetes patients / 北京大学学报(医学版)

OBJECTIVE@#To investigate the associations of impaired glucose metabolism and insulin resistance with chronic periodontitis in pre-diabetes patients.@*METHODS@#A cross-sectional analysis was conducted and we included a total of 171 pre-diabetes patients aged 30-65 years, free of diabetes. pre-diabetes was defined as impaired fasting glucose (IFG) [fasting glucose (FG): 6.1-7.0 mmol/L] and/or impaired glucose tolerance (IGT) [oral glucose tolerance test (OGTT): 7.8-11.0 mmol/L]. Chronic periodontitis was defined according to Centers for Disease Control and Prevention (CDC)/American Academy of Periodontology (AAP) definition and the patients were divided into mild, moderate, and severe chronic periodontitis groups [mild: at least two interproximal sites with clinical attachment loss (CAL) ≥3 mm and at least two interproxima sites with probing depth (PD) ≥4 mm or 1 site with PD≥5 mm; moderate: at least two interproximal sites with CAL ≥4 mm and at least two interproxima sites with at least two interproximal sites with PD ≥5 mm; severe: at least two interproximal sites with CAL ≥6 mm and at least one interproxima site with at least two interproximal sites with PD≥5 mm]. A periodontal examination indexes [plaque index (PLI), PD, CAL, and bleeding on probing (BOP)] and glucose metabolism indexes [FG, OGTT, hemoglobinA1c (HbA1c), fasting insulin and homeostasis model assessments of insulin resistance (HOMA-IR)] were measured. The association of glucose metabolism and chronic periodontitis was investigated by multivariable logistic regression analysis.@*RESULTS@#FG in the moderate and severe chronic periodontitis groups was significantly higher compared with mild chronic periodontitis group, HOMA-IR in the moderate and severe chronic periodontitis groups was significantly higher compared with mild chronic periodontitis group, OGTT in the severe chronic periodntitis group was significantly higher compared with mild chronic peridontitis group and moderate chronic periodontitis groups, and there was no significant difference between moderate and mild chronic periodontitis groups. For the insulin and HbA1c, there was no significant difference among mild, moderate and severe chronic periodontitis groups. After multivariable adjustment of age, gender, smoking status, hypertension and body mass index, IFG (OR=1.39, 95%CI: 1.01-1.98) and HOMA-IR (OR=1.36, 95%CI: 1.04-1.76) were associated with moderate periodontitis; IFG (OR=1.64, 95%CI: 1.17-2.40), IGT (OR=1.65, 95%CI: 1.21-2.26), and HOMA-IR (OR=1.72, 95%CI: 1.23-2.41) were significantly associated with severe periodontitis.@*CONCLUSION@#Our data provided evidences that impaired glucose metabolism were associated with chronic periodontitis among pre-diabetes patients.

Analysis of chronic kidney disease staging with different estimated glomerular filtration rate equations in Chinese centenarians / 中华医学杂志(英文版)

BACKGROUND@#Accurate estimation of the glomerular filtration rate (GFR) and staging of chronic kidney disease (CKD) are important. Currently, there is no research on the differences in several estimated GFR equations for staging CKD in a large sample of centenarians. Thus, this study aimed to investigate the differences in CKD staging with the most commonly used equations and to analyze sources of discrepancy.@*METHODS@#A total of 966 centenarians were enrolled in this study from June 2014 to December 2016 in Hainan province, China. The GFR with the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Berlin Initiative Study 1 (BIS1) equations were estimated. Agreement between these equations was investigated with the κ statistic and Bland-Altman plots. Sources of discrepancy were investigated by partial correlation analysis.@*RESULTS@#The κ values of the MDRD and CKD-EPI equations, MDRD and BIS1 equations, and CKD-EPI and BIS1 equations were 0.610, 0.253, and 0.381, respectively. Serum creatinine (Scr) explained 10.96%, 41.60% and 17.06% of the variability in these three comparisons, respectively. Serum uric acid (SUA) explained 3.65% and 5.43% of the variability in the first 2 comparisons, respectively. Gender was associated with significant differences in these 3 comparisons (P < 0.001).@*CONCLUSIONS@#The strengths of agreement between the MDRD and CKD-EPI equations were substantial, but those between the MDRD and BIS1 equations and the CKD-EPI and BIS1 equations were fair. The difference in CKD staging of the first 2 comparisons strongly depended on Scr, SUA and gender, and that of CKD-EPI and BIS1 equations strongly depended on Scr and gender. The incidence at various stages of CKD staging was quite different. Thus, a new equation that is more suitable for the elderly needs to be built in the future.

Analysis of Chemical Constituents of Volatile Oils in Menthae Haplocalycix Herba-Schizonepetae Herba and Herbal Pairs and Comparison of Anti-bacterial Effects in Vitro / 中国实验方剂学杂志

Objective: To discuss the effect of herbal compatibility on the components of volatile oils in Menthae Haplocalycix Herba and Schizonepetae Herba,and the comparison of the anti-bacterial effects in vitro,in order to provide the experimental basis for investigating the effective material basis of their herb-pair. Method: Steam distillation was used to extract volatile oils of Menthae Haplocalycix Herba, Schizonepetae Herba,and their combination. GC-MS was employed to analyze their volatile oils,and the anti-bacterial effects in vitro were compared. Result: Totally 50 compounds were identified from the volatile oils of Menthae Haplocalycix Herba;41 compounds were identified from the volatile oils of Schizonepetae Herba;and 60 compounds were identified from the volatile oils of their herbal pairs. A total of 27 common compounds were found in the samples of three volatile oils. Totally 5 new compounds were detected in the volatile oils of their herbal pairs,and 9 compounds were not detected. In vitro,volatile oils of both their herbal pairs and individual herbs had bacteriostatic effects on dung Enterococcus (ATCC2922),Staphylococcus aureus (ATCC2923),Escherichia coli (ATCC35218),and E. coli (ATCC25922). Among them,volatile oils of their herbal pairs had stronger bacteriostatic effects on dung enterococcus (ATCC2922) and staphylococcus aureus (ATCC2923) than volatile oils of individual herbs. Moreover,the order of the inhibitory effects of volatile oils on E. coli (ATCC35218 and ATCC25922) were "herbal pairs=peppermint > herba schizonepetae". Conclusion: There were some changes between the volatile oils of individual herbs and the volatile oils of their herbal pairs. These phenomena may be caused by the occurrence of certain chemical reactions and physical changes in compatibility of decocting process. The antibacterial effects of volatile oils of their herbal pairs were better than those of individual herbs in vitro.